Antioxidants may protect against the development of esophageal adenocarcinoma. Blood samples and endoscopic biopsies (squamous, Barrett's, and gastric mucosa) were obtained from 48 Barrett's esophagus (BE) patients, while 48 age- and sex-matched controls provided blood samples only. Plasma concentrations of vitamins A, C, and E were measured in all subjects, while vitamin C was measured in relation to the type of mucosa. Plasma total vitamin C level, but not vitamin A or E, was lower in BE patients compared to controls (P = 0.014). Tissue levels of total vitamin C were significantly lower in Barrett's compared with squamous mucosa (P = 0.047). A positive association was observed between plasma vitamin C and dietary intake of vitamin C, while there was an inverse association with alcohol consumption. The lower levels of vitamin C in plasma of BE patients and in Barrett's mucosa compared with squamous mucosa are consistent with oxidative stress being of importance in the pathogenesis and neoplastic progression of BE.